Integrated analysis of the critical region 5p15.3–p15.2 associated with cri-du-chat syndrome
Cri-du-chat syndrome (CdCs) is caused by a deletion of the distal part of the short arm of chromosome 5. The clinical characteristics of CdCs are well known and include a cat-like cry, psychomotor delay, intellectual disability, microcephaly and dysmorphic facial features. Many patients also have abnormalities in the heart and other systems. However it is still unclear which genes or combination of genes may be responsible for these defects. Analyzing six patients with typical manifestations of the syndrome the authors found that all six had a 10.8 Mb smallest region of overlap (SRO) in the 5p15.33p15.2 segment. This area of 5p contains 44 genes.
Further analysis (including topological analysis) showed that genes SLC6A3, TPPP and CCT5 from the SRO region may be responsible for neuronal development. The changes to the SLC6A3 and TPPP-coded proteins could result in neuronal changes associated with hyperactivity, anxiety, and depression. Moreover, SLC6A3 also interacts with CCT5 and is associated with processes that include memory and learning.
The deficiency of genes CTNND2, TERT, and MED10 may be the primary contributor in regards to the behavioral and cognitive impairments seen in CdCs patients. These three genes affect processes related to neurogenesis, DNA repair, and apoptosis.
Network analysis indicated that the genes MTRR, CEP72, NDUFS6, MRPL36, and MED10 may be associated with the development of congenital heart defects, microcephaly, and other abnormalities in CdCs. These genes were found to be associated with processes that included DNA repair, cell cycle control, apoptosis, ATP synthesis, and electron transport.
Corrêa T, Feltes BC, Riegel M. Integrated analysis of the critical region 5p15.3-p15.2 associated with cri-du-chat syndrome. Genet. Mol. Biol. 2019, ahead of print.
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